The structures of the transition states for a variety of important biochemical reaction types are being investigated, chiefly by such isotope-effect probes as the beta deuterium isotope effect, for both the enzymically catalyzed process and closely related models. These data should help to reveal how enzymes catalyze reactions through interaction with and possible alteration of transition-state structures. Solvent isotope effects, including "proton inventories", are also employed as probes of protonic bridging interactions between enzyme functions and substrate features.